Since its inception in 1993, the ARC at the LSUHSC has grown and matured. In the beginning, our overall theme was the effects of alcohol on immune responses and host defense. With the emergence of the HIV epidemic and the importance of defining cofactors that might affect host susceptibility to infection and/or disease progression, we then focused our efforts on the role of alcohol in HIV infection and progression. These issues are of particular relevance to Louisiana which ranks high in both alcohol consumption and the number of HIV infected citizens. To this end, we developed a model of chronic alcohol administration in rhesus macaques infected with SIV. By all accounts, this is the best available animal model of HIV infection. We found that alcohol significantly increases the viral set point in SIV infected monkeys which is reported to be the most reliable predictor of disease progression in the SIV-macaque model. We believe that these data are both novel and important and we intend to now explore the underlying mechanisms involved.

Realizing that the rhesus macaque model is a unique and precious resource and that both alcohol and HIV cause multisystem disease, we designed our studies so that several other investigations could be performed in parallel with our prospective study of the effects of alcohol on SIV infection and progression. Dr. Peter Winsauer examines the question as to whether alcohol administration exacerbates the neuropsychological deficits observed in subjects infected with HIV. He recently reported that alcohol administration in our SIV-macaque model produced greater behavioral deficits than either alcohol or SIV alone. Dr. Winsauer plans to determine how SIV and ethanol interact to produce the observed disruptions in behavior. Dr. Patricia Molina examines the effects of alcohol on AIDS-associated muscle wasting.

We have also recruited established SIV research scientists into alcohol-related research in order to expand our studies on the effects of alcohol on HIV infection and disease progression. In collaboration with Dr. Ron Veazey, Director of Pathology at the Tulane National Primate Research Center, we are conducting studies to determine whether chronic alcohol consumption results in an increased rate of mucosal SIV transmission and if alcohol increases the number of viral target cells, particularly those in the intestinal tract. Dr. Andrew MacLean examines the effects of alcohol on HIV invasion across the blood-brain barrier.

In summary, we believe that we have successfully developed a model system that can address a wide range of issues relevant to the health consequences of alcohol and HIV infection. Our present investigations concern the effects of alcohol on susceptibility to SIV infection and disease progression, neuropsychological functioning, muscle wasting, mucosal transmission, and the neuropathogenesis of AIDS. We propose to expand our present investigations into underlying mechanisms and treatment utilizing this model system.

In order to compliment our rhesus macaque studies and to identify new research target areas, we also utilize rodent models of alcohol intoxication and infection. Rodent models permit us to utilize state-of-the-art scientific methodologies (gene transfer, transgenic models, knockouts) to determine how alcohol disrupts normal immune function such as cytokine/chemokine pathways that are relevant to HIV infected patients who abuse alcohol. Both Dr. Judd Shellito and Dr. Stephen Kantrow employ rodent models to define basic immune mechanisms involved in infection and how they are disrupted by alcohol administration. We then plan to propose new hypotheses based on these data that can be tested in our rhesus macaque SIV model.

In 1999 we started a research partnership with Xavier University, a highly regarded Historically Black College/University. The purpose of this collaboration is to promote alcohol research expertise and infrastructure development at Xavier University. Since its inception, several members of the Xavier faculty have been working in our ARC laboratories at LSU over the past few years. These individuals have made significant progress in developing their basic research skills and have presented their work at national and international meetings.

In addition to our biomedical research initiative, the ARC and Xavier are developing a community outreach program. Dr. Kishore is the Principal Investigator of this project which is a community healthcare center-based alcohol abuse prevention study. The project is based in several medical clinics in New Orleans that primarily serve an inner city African American population. The purpose of the study is to test the effectiveness and applicability of prevention/intervention strategies delivered by pharmacists in this patient population.